Fasching PA, Yadav S, Hu C, et al. - In a prospective cohort of patients with metastatic breast cancer (mBC), researchers evaluated mutation rates for breast cancer (BC) predisposition genes, the clinical features of patients with mutations, and the influence of mutations on patient outcome. Researchers assessed germline DNA from 2,595 patients with mBC enrolled in the prospective PRAEGNANT registry for mutations in cancer predisposition genes. They evaluated relationships between mutation status and tumor features, progression-free survival, and overall survival. In 10.4% of patients, germline mutations in 12 established BC predisposition genes (including BRCA1 and BRCA2) were found. In 5.0% of patients, mutation in BRCA1 or BRCA2 was found. A higher proportion of brain metastasis (27.1%) was found in BRCA1 mutation carriers vs nonmutation carriers (12.8%), though mutations did not significantly modify progression-free survival or overall survival for patients with mBC. In all patients with mBC, multigene panel testing may be considered due to the high frequency of germline mutations in BRCA1/2 and other BC predisposition genes. Differences observed in tumor features have implications for treatment and for future studies of targeted therapies, even though the prognosis of mutation carriers and nonmutation carriers with mBC was comparable. A higher proportion of brain metastasis (27.1%) was seen in BRCA1 mutation carriers vs nonmutation carriers (12.8%).